Allergic asthma is a major public health problem, and the morbidity and motility of asthma have increased in the last two decades, particularly in children. The need for safe and effective asthma treatment is greater than ever. Although millions of asthma patients in the US are currently using "herbal therapies," there is little information regarding the efficacy, safety or mechanism[s] of action of herbal anti-asthma formulas. It has been shown that allergic asthma is associated with elevation of serum IgE, airway inflammation and airway hyperresponsiveness (AHR) in both asthmatic patients and animal models. Th 2-type cytokines such as IL-4, IL-5 and IL-13 play a central role in the pathogenesis of allergic asthma. To investigate the effect of herbal interventions for asthma therapy, we evaluated effects of a Chinese herbal formula, MSSM-002, on allergic airway responses using a well-characterized murine model of asthma. MSSM-002, developed in our laboratory, is based on Ja Wai San Zi Tang, used in the China-Japan Friendship Hospital in Beijing, to treat asthma and bronchitis in children. We found that MSSM-002 treatment reduced late-phase AHR, eosinophilic inflammation, mucus production, and IgE and Th2 cytokine production. Suppression of late-phase AHR by MSSM-002 was comparable to that of the potent corticosteroid, dexamethasone, and significantly greater than three commercially available Ma-Huang-containing herbal products. These preliminary results suggest that MSSM-002 has potential as an effective and safe treatment for human asthma. The objective of this project is to further investigate the therapeutic and immunoregulatory mechanisms underlying these effects. We will evaluate whether MSSM-002 can reverse maximally severe AHR, and exert a long-term as well as an acute effect on AHR. We will rigorously control the quality of herbs and consistency of the herbal formula using reproducible analytic methods such as HPLC and TLC, and further assess any possible toxicity utilizing histological and biochemical analyses. Based on our preliminary results, we hypothesize that, in contrast to the generalized immunosuppression produced by corticosteroids, MSSM-002 has specific immunomodulatory effects down-regulating the Th2 response and/or up-regulating the Thl response, which may underlie the observed reduction of AHR and inflammation by MSSM-002. We will further investigate the effects of MSSM-002 on in vivo and in vitro T cell cytokine production. We further hypothesize that MSSM-002 may exert beneficial regulatory effect on co-stimulatory molecules such as B7-1/B7-2 by antigen-presenting cells, which may be the upstream mechanisms of MSSM-002 regulating T cell responses. To move our study one step closer to human studies, we also plan to test the in vitro effects of MSSM-002 on human T cell responses. Accomplishing these goals should provide an experimental basis for applying Chinese herbal medicines to the treatment of allergic asthma, and for understanding immunoregulatory mechanisms underlying their effects.